5-chloro-N-(2-fluoro-5-nitrophenyl)-2-hydroxybenzamide | 1417658-23-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 5-chloro-N-(2-fluoro-5-nitrophenyl)-2-hydroxybenzamide
• 英文别名: 5-chloro-N-(2-fluoro-5-nitro-phenyl)-2-hydroxy-benzamide
• CAS: 1417658-23-1
• 化学式: C₁₃H₈ClFN₂O₄
• 分子量: 310.669
• InChiKey: QTYRVIWHEZBYLO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  95.2
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-chloro-N-(2-fluoro-5-nitrophenyl)-2-hydroxybenzamide 在 氯化铵 、 溶剂黄146 、 锌 作用下， 以 甲醇 、 水 为溶剂， 反应 28.5h， 生成 5-chloro-N-(5-(cyclopentylamino)-2-fluorophenyl)-2-hydroxybenzamide
  参考文献：
  名称：

  新型取代的N-（4-氨基-2-氯苯基）-5-氯-2-羟基苯甲酰胺类似物作为有效的人腺病毒抑制剂的发现

  摘要：

  在免疫功能低下的患者和社区获得性肺炎的健康个体中，有效治疗人腺病毒（HAdV）的方法仍未满足医疗需求。我们在本文中报道了一系列新颖的取代的N-（4-氨基-2-氯苯基）-5-氯-2-羟基苯甲酰胺类似物作为有效的HAdV抑制剂。化合物6，15，29，40，43，46，47，和54个显示出增加的选择性指数（SI> 100）相比，铅化合物氯硝柳胺，同时保持亚微摩尔到针对的HAdV低微摩尔效力。初步的机理研究表明，化合物6化合物46和47可能抑制HAdV生命周期的后续步骤，而43和43可能靶向HAdV DNA复制过程。值得注意的是，在这些衍生物中，化合物15的抗HAdV活性提高（IC 50 = 0.27μM），细胞毒性显着降低（CC 50 = 156.8μM），体内毒性低（仓鼠最大耐受剂量= 150 mg / kg）与尼克洛沙胺相比，支持其进一步治疗HAdV感染的体内功效研究。

  DOI：

  10.1021/acs.jmedchem.0c01226
• 作为产物：
  描述：

  5-chloro-N-(2-fluoro-5-nitrophenyl)-2-methoxybenzamide 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 以370 mg的产率得到5-chloro-N-(2-fluoro-5-nitrophenyl)-2-hydroxybenzamide
  参考文献：
  名称：

  Structure–Activity Relationship Studies on Diversified Salicylamide Derivatives as Potent Inhibitors of Human Adenovirus Infection

  摘要：

  The effective treatment of adenovirus (HAdV) infections in immunocompromised patients still poses great challenges. Herein, we reported our continued efforts to optimize a series of salicylamide derivatives as potent inhibitors of HAdV infection. Of these, nine compounds (11, 13, 14, 17, 20, 58, 60, 62, and 70) showed significantly improved anti-HAdV activities with nanomolar to submicromolar IC50 values and high selectivity indexes (SI > 100), indicating better safety windows, compared to those of the lead compound niclosamide. Our mechanistic assays suggest that compounds 13, 62, and 70 exert their activities in the HAdV entry pathway, while compounds 14 and 60 likely target the HAdV DNA replication, and 11, 17, 20, and 58 inhibit later steps after DNA replication. Given the broad anti-viral activity profile of niclosamide, these derivatives may also offer therapeutic potential for other viral infections.

  DOI：

  10.1021/acs.jmedchem.9b01950

文献信息

• Structure–activity relationships of antitubercular salicylanilides consistent with disruption of the proton gradient via proton shuttling
  作者：Ill-Young Lee、Todd D. Gruber、Amanda Samuels、Minhan Yun、Bora Nam、Minseo Kang、Kathryn Crowley、Benjamin Winterroth、Helena I. Boshoff、Clifton E. Barry

  DOI：10.1016/j.bmc.2012.10.056

  日期：2013.1

  A series of salicylanilides was synthesized based on a high-throughput screening hit against Mycobacterium tuberculosis. A free phenolic hydroxyl on the salicylic acid moeity is required for activity, and the structure-activity relationship of the aniline ring is largely driven by the presence of electron withdrawing groups. We synthesized 94 analogs exploring substitutions of both rings and the linker region in this series and we have identified multiple compounds with low micromolar potency. Unfortunately, cytotoxicity in a murine macrophage cell line trends with antimicrobial activity, suggesting a similar mechanism of action. We propose that salicylanilides function as proton shuttles that kill cells by destroying the cellular proton gradient, limiting their utility as potential therapeutics. Published by Elsevier Ltd.
• Discovery of Novel Substituted <i>N</i>-(4-Amino-2-chlorophenyl)-5-chloro-2-hydroxybenzamide Analogues as Potent Human Adenovirus Inhibitors
  作者：Jimin Xu、Judith Berastegui-Cabrera、Na Ye、Marta Carretero-Ledesma、Jerónimo Pachón-Díaz、Haiying Chen、Maria Eugenia Pachón-Ibáñez、Javier Sánchez-Céspedes、Jia Zhou

  DOI：10.1021/acs.jmedchem.0c01226

  日期：2020.11.12

  for human adenovirus (HAdV) infections in immunocompromised patients and healthy individuals with community-acquired pneumonia remains an unmet medical need. We herein reported a series of novel substituted N-(4-amino-2-chlorophenyl)-5-chloro-2-hydroxybenzamide analogues as potent HAdV inhibitors. Compounds 6, 15, 29, 40, 43, 46, 47, and 54 exhibited increased selectivity indexes (SI > 100) compared

  在免疫功能低下的患者和社区获得性肺炎的健康个体中，有效治疗人腺病毒（HAdV）的方法仍未满足医疗需求。我们在本文中报道了一系列新颖的取代的N-（4-氨基-2-氯苯基）-5-氯-2-羟基苯甲酰胺类似物作为有效的HAdV抑制剂。化合物6，15，29，40，43，46，47，和54个显示出增加的选择性指数（SI> 100）相比，铅化合物氯硝柳胺，同时保持亚微摩尔到针对的HAdV低微摩尔效力。初步的机理研究表明，化合物6化合物46和47可能抑制HAdV生命周期的后续步骤，而43和43可能靶向HAdV DNA复制过程。值得注意的是，在这些衍生物中，化合物15的抗HAdV活性提高（IC 50 = 0.27μM），细胞毒性显着降低（CC 50 = 156.8μM），体内毒性低（仓鼠最大耐受剂量= 150 mg / kg）与尼克洛沙胺相比，支持其进一步治疗HAdV感染的体内功效研究。
• Structure–Activity Relationship Studies on Diversified Salicylamide Derivatives as Potent Inhibitors of Human Adenovirus Infection
  作者：Jimin Xu、Judith Berastegui-Cabrera、Haiying Chen、Jerónimo Pachón、Jia Zhou、Javier Sánchez-Céspedes

  DOI：10.1021/acs.jmedchem.9b01950

  日期：2020.3.26

  The effective treatment of adenovirus (HAdV) infections in immunocompromised patients still poses great challenges. Herein, we reported our continued efforts to optimize a series of salicylamide derivatives as potent inhibitors of HAdV infection. Of these, nine compounds (11, 13, 14, 17, 20, 58, 60, 62, and 70) showed significantly improved anti-HAdV activities with nanomolar to submicromolar IC50 values and high selectivity indexes (SI > 100), indicating better safety windows, compared to those of the lead compound niclosamide. Our mechanistic assays suggest that compounds 13, 62, and 70 exert their activities in the HAdV entry pathway, while compounds 14 and 60 likely target the HAdV DNA replication, and 11, 17, 20, and 58 inhibit later steps after DNA replication. Given the broad anti-viral activity profile of niclosamide, these derivatives may also offer therapeutic potential for other viral infections.